Disease- and treatment-related predictors of hepatic mitochondrial dysfunction in chronic HIV infection assessed by non-invasive (13)C-methionine breath test diagnostic.
OBJECTIVE
An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons are due to hepatic complications. Hepatitis coinfection, antiretroviral treatment and co-occurrence of metabolic risk factors contribute to hepatic mitochondrial damage manifesting in hepatic steatosis and steatohepatitis. The aim was to assess disease- and treatment-related predictors on hepatic mitochondrial dysfunction in HIV infection by means of a new (13)C-methionine breath test (MeBT).


METHODS
148 HIV positive individuals with and without antiretroviral treatment (ART) [44 therapy-naives; 89 patients on combination ART and 15 patients on structured treatment interruption (STI)] and 20 HIV-negative controls were studied prospectively by MeBT.


RESULTS
A decay of (13)C-methionine metabolism, expressed as cumulated percentage dose recovered over 1.5h (cPDR(1.5h)), in the subgroups of treatment-naives and patients on STI compared to controls was detected (cPDR(1.5h): 3.4 +/- 1.3% and 4.0 +/- 2.4% vs. 6.3 +/- 1.2%; p<0.01). Multivariate analyses including metabolic, treatment- and disease-related variables showed that antiretroviral treatment with stavudine, didanosine or zalcitabine and treatment-naivety were best predictors of a reduced MeBT result (cPDR(1.5h)) (beta = -0.56 and -0.50, p<0.05). CD4 count had only a minor association (beta = 0.15, p<0.05). No other variable including disease and treatment duration was associated with MeBT outcome. These factors explained 39% of the variance of MeBT results (p<0.05).


CONCLUSIONS
Therapy naivety and treatment with d-drugs were the best predictors of poor MeBT outcome. MeBT may be proposed as a feasible, noninvasive diagnostic instrument for clinical assessment of hepatic mitochondrial function and early detection of drug-induced mitochondriotoxity in chronic HIV infection.
Banasch
M
M
Department of Internal Medicine, St Josef-Hospital, University of Bochum, Bochum, Germany. mbanasch@gmx.de
Knyhala
K
K
Kollar
S
S
Serova
K
K
Potthoff
A
A
Schlottmann
R
R
Schmidt
W E
WE
Brockmeyer
N H
NH
Goetze
O
O
D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D001944:Breath Tests / Q000379:methods*; D002247:Carbon Isotopes; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000175:diagnosis*; D011237:Predictive Value of Tests
D044966:Anti-Retroviral Agents; D002247:Carbon Isotopes; D008715:Methionine